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Cirrhosis-Associated RAS-Inflammation-Coagulation Axis Anomalies: Parallels to Severe COVID-19

Lukas Hartl1,2, Mathias Jachs1,2, Benedikt Simbrunner1,2,3

  • 1Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria.

Journal of Personalized Medicine
|December 24, 2021
PubMed

Insights

Cirrhotic patients show increased renin-angiotensin-aldosterone system (RAS) activity, inflammation, and endothelial dysfunction, mirroring severe COVID-19. These changes in cirrhosis patients are linked to liver disease severity and correlate with COVID-19 patient profiles.

Area of Science:

  • Hepatology
  • Cardiovascular Science
  • Infectious Disease

Background:

  • Cirrhotic patients face higher risks for severe COVID-19.
  • Investigated the renin-angiotensin-aldosterone system (RAS), endothelial dysfunction, inflammation, and coagulation/fibrinolysis in cirrhosis and COVID-19 patients.

Purpose of the Study:

  • To investigate the renin-angiotensin-aldosterone system (RAS) and related physiological parameters in cirrhotic patients.
  • To compare these parameters with those in COVID-19 patients, including those with acute respiratory distress syndrome (ARDS).

Main Methods:

  • 127 cirrhotic patients (CIRR), 9 mild COVID-19, 11 ARDS-COVID, and 10 healthy subjects (HS) were studied.
  • Portal hypertension (PH) assessed via hepatic venous pressure gradient (HVPG).
  • Measured RAS activity, endothelial dysfunction markers, inflammatory markers, and coagulation/fibrinolysis parameters.

Main Results:

  • Cirrhotic patients showed increased RAS activity (ACE, renin, aldosterone), endothelial dysfunction (VWF antigen), inflammation (CRP, IL-6), and disturbed coagulation/fibrinolysis (F1,2, D-dimer, plasminogen, antiplasmin) with increasing liver disease severity.
  • COVID-19 patients exhibited altered RAS activity, endothelial dysfunction, coagulation, and inflammation, with trends similar to cirrhosis severity.
  • In cirrhosis, ACE activity correlated with IL-6, VWF antigen, and inversely with prothrombin fragment F1,2 and antiplasmin activity.

Conclusions:

  • Upregulation of RAS in Child-Pugh B/C cirrhosis is associated with systemic inflammation, endothelial dysfunction, and abnormal coagulation.
  • Cirrhosis-associated abnormalities in ACE, IL-6, VWF antigen, and antiplasmin resemble those seen in severe COVID-19.
  • These findings highlight shared pathophysiological mechanisms between severe cirrhosis and severe COVID-19.

Keywords:
acute respiratory distress syndromefibrinolysisinflammationportal hypertensionrenin-angiotensin-system

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